1. Field of the Invention
This invention relates to microbiological processes for preparation of prodigiosin. More particularly, this invention relates to a process for preparation of prodigiosin by using a novel bacterial strain and a process therefor using a novel synthetic culture medium.
2. Description of the Prior Art
Prodigiosin is an antibiotic having antimicrobial activity against bacteria, fungi, protozoa and the like. Its clinical experiment on coccidioidomycosis has been reported [R. H. Wier et al., Am. J. Med. Sci. 224, 70 (1952)]. As to its toxicity, it has been reported that thrombosis was observed only at the site when a colloidal preparation comprising crystalline prodigiosin sample, ascorbic acid and glucose was intravenously administered [G. V. Taplin et al.: Am. J. Roentgenol. Radium Ther. Nucl. Med. 71, 294(1954)]. According to recent researches, prodigiosin has been reported to be a useful antibiotic which has little toxic effects on embryos [G. S. Kalesperis et al., Can. J. Microbiol. 21, 213 (1974)]. It is also known that prodigiosin has antitumor activity.
Prodigiosin has been produced by microbiological methods wherein the strains used include Chromobacterium prodigiosum (Serratia marcescens) ["Merck Index" 8th ed. (1968)] and B. prodigiosus (Serratia marcescens) ["Integrated English-Japanese Medical Dictionary," Nanzando (1971)]. These known strains, however, do not always exhibit a capability of producing prodigiosin in high yields. Thus, a strain having a capability of producing prodigiosin in high yields has been desired in the art.
On the other hand, a variety of culture media have been proposed for the microbiological processes. Solid media containing agar was employed, but the cultivation on a large scale was difficult. Liquid media took the place of the solid media. Among these media was a glycerol-peptone medium that produced prodigiosin most efficiently [M. I. Bunting: Cold Spring Harbor Symposia Quant. Biol. 11, 25 (1946)]. Problems reside in that it is a natural medium and requires expensive materials for the medium. However, all the other culture media including synthetic media did not provide as high industrial productivity of prodigiosin as the glycerol-peptone medium.
It has also been reported that the yield of prodigiosin was promoted when a certain higher unsaturated fatty acid such as oleic acid was incorporated into a certain medium [A. W. Linnane et al.: Australian J. Sci. 16, 27 (1953)].